Infertility affects approximately 12% of women aged 15-44 years;this prevalence increases to about 30% in women over age 35 years. In 2002, approximately 1% of all babies born in the US were a result of in- vitro fertilization (IVF). The gonadotropin drugs used in ovarian stimulation are potent, and lead to estrogen levels as much as 5-15 times higher than those typical for reproductive-age women. Multiple stimulation cycles have become increasingly common, especially since the mid to late nineties, as clinics have attempted to reduce the number of embryos transferred during IVF. Although health effects of hormonal treatments such as oral contraceptives and postmenopausal hormone therapy have been well- documented, surprisingly little is known regarding the long-term consequences of infertility treatments. Thus, we propose to conduct a pilot study exploring the possibility of initiating research on infertility treatment in relation to long-term health within participants of the ongoing Nurses'Health Study II. The Nurses'Health Study II includes 118,000 women, aged 25-42 years when the study started in 1989;since 1995, 9,200 women have reported a history of infertility, with 1,900 reporting use of gonadotropin drugs. The Nurses'Health Study II cohort has important advantages in studying infertility treatment, since confounding due to healthcare knowledge and access may be minimized in these health professionals. Specifically, we propose to: (1) develop and validate a supplementary questionnaire for participants with a history of infertility, to collect data on treatment history and utilization, and other relevant information;and (2) conduct preliminary analyses, including exploration of any increased risk of hypertension associated with gonadotropin use, and any increased risk of benign breast disease (both of these are common outcomes, with adequate power to detect relations after a modest follow-up period). Overall, this proposed pilot study has the potential to lead to substantial research on a wide variety of issues related to IVF and infertility treatment. For example, within the Nurses'Health Study II, we could eventually consider further outcomes, such as vascular biomarkers, taking advantage of blood samples which were collected from the subjects. In addition, over the years, with further follow-up, we could examine clinical cardiovascular disease, various cancers, etc. PUBLIC HEALTH RELEVANCE: Infertility affects approximately 12% of women aged 15-44 years. In 2002, one % of babies born in the US were a result of in-vitro fertilization (IVF). The gonadotropin drugs used in ovarian stimulation are potent, and lead to estrogen levels as much as 5-15 times higher than those typical for reproductive- age women. Although health effects of hormonal treatments such as oral contraceptives have been well-documented, little is known regarding the long-term consequences of infertility treatments. Thus, we propose to conduct a pilot study exploring the possibility of initiating research on infertility treatment in relation to long-term health within participants of the ongoing Nurses'Health Study II.